Merck suffers late-stage blow to vorapaxar
pharmafile | January 18, 2011 | News story | Research and Development | ACS, Merck & Co, acute coronary syndrome, anticoagulant, heart attack, peripheral arterial disease, stroke, vorapaxar
An increased risk of bleeding caused by pipeline drug vorapaxar has dealt Merck a major blow.
The Data and Safety Monitoring Board overseeing the study of the drug in acute coronary syndrome (ACS) patients says one phase III study should be halted and another study should only continue in a sub-group of patients.
The anticoagulant is aimed at preventing a second heart attacks or stroke in people who had already suffered one, but the results suggest it raises the risk of strokes because of excess bleeding.
The results are bad news for Merck’s pipeline prospects, as vorapaxar was seen as one of the company’s brightest prospects. Analysts had predicted the drug could reach annual sales of over $3 billion, but the developments raise doubts about whether the drug will ever win approval.
The chairman of the TRA-2P study Dr. Eugene Braunwald said: “They [the Data and Safety Monitoring Board] have observed an increase in intracranial haemorrhage in patients with a history of stroke that is not outweighed by their considerations of potential benefit.”
This means the TRACER study is to be wound up, while patients on the TRA-2P study who had suffered a stroke before taking part in the study or during the study will have treatment immediately discontinued. The study will continue to run only in patients who had suffered a previous heart attack or peripheral arterial disease (around 75% of participants).
Vorapaxar is a thrombin receptor (PAR-1) antagonist based on himbacine, a compound found in the bark of magnolia trees. There is one other notable drug in the same class in development – Eisai’s atopaxar, which is currently in phase II studies.
TRACER is a hospital-based study of around 13,000 patients with non-ST-segment-elevation ACS. In TRACER, vorapaxar was administered starting with a 40 mg loading dose, followed by a 2.5 mg daily dose.
TRA-2P, or TIMI 50, is a chronic care, secondary prevention study of around 26,500 patients who have experienced a heart attack, an ischemic stroke, or have documented peripheral vascular disease. In TRA-2P, vorapaxar is administered at a 2.5 mg daily dose. The primary endpoint of TRA-2P is the first occurrence of any component of the composite of cardiovascular death, MI, stroke, and urgent coronary revascularisation compared to placebo.
Competition in the cardiology field to treat ACS has become intense in recent years, and a number of new drugs are competing for a share of the market. Another new competitior is AstraZeneca’s Brilinta (ticagrelor) which is currently awaiting FDA approval.
The market for treating ACS has been established by Sanofi-Aventis/BMS’s drug Plavix (clopidogrel), but the blockbuster loses its US patent in 2012.
Pfizer and BMS’ apixaban, a novel anticoagulant was also being studied for use in ACS, but suffered a similar fate to vorapaxar when its trial was stopped in November 2010.
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